A significant interaction exists between mineral cations and basic amino acids in physiological fluids. Deficiencies of potassium result in intracellular accumulation of lysine and other basic amino acids whereas excess potassium has the opposite effect. Recent studies in this laboratory indicate that the activity of an enzyme of lysine catabolism, lysine-alpha-ketoglutarate reductase (LKR) is increased by excessive dietary potassium, and that this effect is associated with marked reduction in the growth-depressing effect of excess dietary lysine. Chloride appears to have the reverse effect. It is possible, therefore, that the metabolism of basic amino acids is linked to the regulation of iron balance. This proposal will determine whether variations in dietary K, Na, Ca, Mg, Cl and P alter the metabolism of lysine, arginine, ornithine and influence the toxicity of, and nutritional requirements for, these amino acids. Growing chicks will be fed diets containing excessive or limiting amounts of these amino acids and varying in mineral cations and anions. Growth, food consumption, and activities of LKR, arginase, ornithine-delta-transaminase and histidase will be determined. Adrenalectomy and hormone administration will test the possible role of insulin, glucagon and adrenal hormones in mineral-induced changes in enzyme activity. Tissue and blood levels of minerals will be assayed by ion selective electrodes and atomic absorption spectroscopy and amino acids will be measured using an amino acid analyzer. Strains of chicks which are hyperlysinemic and differ in hepatic LKR and ornithine-delta-transaminase will be investigated with regard to possible mineral involvement in the genetic differences. Current studies indicate that LKR is phosphate dependent in vitro, and that phosphate concentration is critical in detecting differences which are evident in vivo. The enzyme will be purified and the nature of the phosphate requirement and its possible role in the regulation of the enzyme will be determined.